This invention relates to an improved process for treating fermentation broths in which a solid particulate form of encapsulated antifoam is employed in a bioreactor vessel in order that fouling be reduced in ultrafiltration equipment employed downstream of the bioreactor vessel during concentration of the broth.
Fermentation processing involves organisms such as bacteria, yeast, and fungus, in a culture medium of a broth including starch, glucose, oxygen, and various proteins. The aqueous broth is allowed to ferment for a number of days, and as the broth is fermenting, the broth is supplied with a constant amount of oxygen in order to increase the rate of aerobic conversion. As a result of such oxygen sparging, and because of the presence of surface active proteins, a substantial amount of foam is produced in the bioreactor vessel. It has therefore been conventional practice to add a foam inhibitor to the broth in order to reduce the accumulation of foam. Traditionally, such foam inhibitors have been in the form of emulsions including droplets of oil dispersed in water. Such emulsion type antifoam formulations have necessarily included surfactants, coagulants, and gelatinous thickeners, for the purpose of stabilizing these antifoam formulations.
Following completion of the microbial activity in the bioreactor, it is necessary to process the fermentation broth by concentrating the broth in order to separate desired products from the impurities contained in the broth. This processing is typically conducted by passing the fermentation broth from the bioreactor to a filtration unit located downstream of the bioreactor. The filtration systems employed are ultrafiltration units employing membranes. In these separation units, there is generated a high pressure bulk flow of broth across hydrophobic membranes having pore sizes ranging from 0.01 to 1.0 micron. The broth passes through the membrane, while the impurities sought to be separated are retarded by the membrane. These impurities constitute, for example, cells, proteins, and bacteria. It has been found that such membranes are highly sensitive to fouling and clogging, with the result that the filtration rate, expressed as flux through the membrane, is inhibited; the product yield is reduced; and there is a corresponding reduction in the life-span of the membrane itself. One contributing factor to membrane fouling, clogging, and filtration rate inhibition, is believed to be the presence in the antifoam emulsion of the various surfactants, coagulants, and thickeners, used to stabilize emulsion type antifoams. These surfactants, coagulants, and thickeners, form a gel layer at the interface of the membrane and the aqueous phase, and the gel layer clings to the surface of the membrane, inhibiting the filtration rate of the effluent therethrough.
Thus, it should be apparent that there exists a need for an antifoam formulation which will effectively inhibit the formation of foam in the fermentation broth in the bioreactor, and which will also allow high efficiency filtration rates through the membrane, and without the formation of flux inhibiting gel layers prone to foul the membrane and reduce its efficiency.
Encapsulated antifoams are not new, nor is the encapsulation of antifoams in water soluble materials new or novel. For example, it has recently been reported that a new process for encapsulating liquids or solids in a cornstarch matrix for slow release has been developed by the USDA Northern Regional Research Center. The matrix consists of a compound produced from amylose and amylopectin. In order to encapsulate a herbicide, for example, cornstarch is cooked in a jet of steam to gelatinize the starch. The herbicide, insect lure, plant growth regulator, fertilizer, medicine, flavoring, coloring, or vitamin, is mixed in; dried; and the mixture may be crumbled or ground to granules or particles, respectively. In United Kingdom Published Unexamined Application No. 2180254, filed Sept. 10, 1986, and published Mar. 25, 1987, a sugar such as sucrose is used in a detergent composition but acts, rather than an encapsulant, to increase the dispersibility of the detergent. In European Published Unexamined Application No. 0171457, filed Aug. 17, 1984, published Feb. 19, 1986, particles of sugar such as lactose are embedded in a semi-permeable membrane and then dissolved, releasing water soluble actives.
In U.S. Pat. No. 3,159,585, issued Dec. 1, 1964, various oils such as vegetable fats are encapsulated with dextrins. Sugar in the form of mixtures of mannitol, sorbitol, and refined cane sugar, are used to encapsulate mineral oil in U.S. Pat. No. 3,779,942, issued Dec. 18, 1973. Fragrance oils, spice oils, perfume oils, and fruit flavors, are taught in U.S. Pat. No. 3,971,852, issued July 27, 1976, to be encapsulated in a mixture of dextrin and a sugar such as sucrose, fructose, and glucose. In U.S. Pat. No. 4,481,157, issued Nov. 6, 1984, a mixture of gelatin, sorbitol, water, and a coagulant, such as a liquid paraffin, is used to encapsulate vegetable oil. A bulk laxative containing methylcellulose particulates encapsulated in sucrose is disclosed in U.S. Pat. No. 4,732,917, issued Mar. 22, 1988.
A silicone antifoam formulation is disclosed in United Kingdom Patent No. 892,787, granted Mar. 28, 1962, and in which an organosiloxane emulsion including fume silica, is spray dried along with methylcellulose in order to form encapsulated antifoam particles. Other encapsulating materials are disclosed to be starch, gelatin, albumen, gum acacia, locust bean gum, carrageena, polyvinyl alcohol, polyethylene glycol, and guar gum.
However, all of the foregoing references require the presence of one or more of a surfactant, coagulant, thickener, or additive, in order to stabilize the system. In addition, none relate specifically to environments including ultrafiltration equipment or membrane separators, nor do the references relate to fluid treatment systems such as fermentation processes requiring such ultrafiltration equipment or membrane separators.
There is described in PCT International Publication No. WO 86/05411, published Sept. 25, 1986, an ultrafiltration system that employs a silicone alkylene oxide copolymer as a foam inhibitor for the fluids processed therein. This antifoam material is allegedly does not permanently foul the membrane, in comparison to conventional antifoam formulations containing additives such as emulsigying agents. It is noted, however, that in the event the membrane does become fouled, that the fouling process can be reversed by cleaning the membrane using conventional techniques such as flushing the membrane with cold water or with a mild bleach solution. The silicone alkylene oxide copolymeric antifoam material of the PCT International Publication is also disclosed to be operable in functioning as a foam inhibitor in the absence of emulsifiers, solvents, and finely divided insoluble matter.
In accordance with the present invention, a novel alternative foam inhibitor is provided, which foam inhibitor is effective for use, for example, in methods for processing aqueous fermentation broths in a bioreactor vessel, in which the broth is conveyed downstream as a feed solution to an ultrafiltration system including a membrane for concentrating the aqueous fermentation broth. The foam inhibitor is in the form of an oil based liquid in the form of droplets, the droplets of the oil based liquid antifoam being dispersed, encased, entrapped, and imbedded, within solid particles of a water soluble encapsulating material. The encapsulated particulate antifoam is free of additives known to inhibit the filtration rate through the membrane, such as surfactants, coagulants, and thickners. When added to the fermentation broth, the bland encapsulating material of the present invention, dissolves and releases the additive free active antifoam ingredient into the aqueous phase in the bioreactor vessel.
Unlike the silicone alkylene oxide copolymer of the PCT International Publication referred to previously, the antifoams of the present invention meet the requirements of and are permissible in most foods, as established under rulings of the United States Food and Drug Administration. Further, the materials of the present invention are in an otherwise solid particulate form, rendering them capable of a programmed form of release of the antifoam encapsulated therein, in contrast to the bulk fluids of the PCT International Publication.